FIG. 1 shows various anatomical structures associated with the head of a horse. Among these, the airway structures, and in particular the larynx, are susceptible to various disorders which affect the horse's health and its ability to perform normally. The larynx is innervated by the recurrent laryngeal nerves (RLN) which contain motor fibers that innervate both the abductor/opener and adductor/closer muscles of the arytenoid cartilages and their associated vocal folds.
Laryngeal hemiplegia is a distal axonopathy affecting the left recurrent laryngeal nerve causing a unilateral disease termed laryngeal hemiplegia/paresis. Damage to the left recurrent laryngeal nerve compromises both of these functions by stopping vocal fold movement in a position just lateral to the midline. The cause of this disease is unknown, although a genetic predisposition is suspected. Other potential causes include direct trauma, lead poisoning, liver disease and viral infection. Despite this left vocal fold paralysis, pulmonary ventilation at rest is adequate because abduction of the opposite arytenoid cartilage can still occur with each inspiration. However, during exercise, the cross sectional area of the larynx is further reduced by further collapse of the affected cartilage during inhalation. This results in significant airflow reduction associated with an abnormal upper respiratory noise at exercise. In horses used for competition, the decreased volume of airflow interferes with performance and may impair the horse's ability to compete. In rare cases, the condition might be bilateral, leading to severe airway obstruction at rest if any enhanced inspiratory drive is present since the arytenoid collapse is increased, leading to dyspnea and possibly death.
Prosthetic laryngoplasty is currently the preferred surgical treatment for laryngeal hemiplegia. The paralyzed left arytenoid cartilage is sutured in an open position to restore airflow. Retrospective analyses on the postoperative performance of racehorses treated with a laryngoplasty revealed a modest success rate but many complications. See, e.g., Kidd J A, Slone D E, Treatment Of Laryngeal Hemiplegia In Horses By Prosthetic Laryngoplasty, Ventriculectomy And Vocal Cordectomy, Vet. Rec. 150:481-484, 2002; Greet T R C, Baker G J, Lee R., The Effect Of Laryngoplasty On Pharyngeal Function In The Horse, Eq. Vet. J., 11:153-158, 1979; Russell A P, Slone D E, Performance Analysis After Prosthetic Laryngoplasty And Bilateral Ventriculectomy For Laryngeal Hemiplegia In Horses: 70 Cases (1986-1991), J. Am. Vet. Med. Assoc., 204:1235-1241, 1994; Hawkins J F et al., Laryngoplasty With Or Without Ventriculectomy For Treatment Of Left Laryngeal Hemiplegia In 230 Horses, Vet. Surg., 26:484-491, 1997; Strand E. et al., Career Racing Performance In Thoroughbreds Treated With Prosthetic Laryngoplasty For Laryngeal Neuropathy: 52 Cases (1981-1989), J. Am. Vet. Med. Assoc., 217:1689-1696, 2000; all incorporated herein by reference.
The main complications of such surgery are associated with insufficient abduction of the left arytenoid cartilage causing continued exercise intolerance in approximately 40% of horses, loosening of the prosthetic suture(s) resulting in some loss of the initial degree of abduction in almost all horses by 6 weeks, and persistent respiratory noise in 25% of horses. See, e.g., Ducharme N G, Hackett R P, What is the True Value of Laryngeal Surgery?, Comp Cont Educ, 13:472-475, 1991; Dixon P M et al., Long Term Survey Of Laryngoplasty And Ventriculocordectomy In An Older Mixed-Breed Population Of 200 Horses. Part 1. Maintenance Of Surgical Arytenoid Abduction And Complications Of Surgery. Eq Vet J 35:389-396, 2003; Dixon P M et al., Long Term Survey Of Laryngoplasty And Ventriculocordectomy In An Older Mixed-Breed Population Of 200 Horses. Part 2: Owner's Assessment Of The Value Of Surgery, Eq Vet J 35:397-401, 2003; Ferraro G L, Laryngeal Hemiplegia In Current Practice Of Equine Surgery, White N A and Moore J N (eds), Philadelphia J.B. Lippincott Co, pp 251-255, 1990, all incorporated herein by reference.
Although these conventional methods of treatment have been useful in some horses, they are clearly less than ideal since they have modest success rates, significant complications, and do not slow the progression of the disease. Thus, it is usually just a matter of months until the disease reaches a state where these methods to not help anymore.
Although many experiments have attempted to develop and many patents exist to describe an implanted electrical treatment system for human laryngeal disorders, there has not been any such system developed for horses. As summarized in Table 1 and explained below, the clinical condition in horses is very different from that of humans and much more technically challenging for an electrical treatment system.
TABLE 1Difference Between Human And Equine Unilateral Laryngeal Hemiplegia.PARAMETERHORSESHUMANSVocal Fold Involved forUnilateralBilateral, because unilateral paralysis inabductor stimulationhuman is not a big handicap for abduction.Vocal Fold LateralityLeftLeft or rightVocal Fold AbductionContinuous prolonged abduction forInspiratory abduction for 1-2 secondshours (as long as the horse is doingany kind of intensive movement);most muscles of any other specieswould fatigue after a few minutes ofcontinuous stimulation.TherapyTracheostomy does not cureTracheostomy curesImpairmentAthletic performance/abnormalMedical/life threatening because of airnoise; no life threatening airimpairmentimpairmentSeveritySlight paresis causes symptomsParalysis needed for symptomsQuiet RespirationNot impairedImpairedAdductionVF adduction can be sacrificedLoss of adduction causes aspiration andweakens or sacrifices voice productionIt is therefore clear, that unilateral hemiplegia are very different conditions, requiring different treatment approaches for success, and an approach that works in one species is not necessarily suitable for the other species. In humans, airway compromise usually occurs when both vocal folds are paralyzed. In contrast, in horses, the condition occurs when a single vocal fold is paralyzed. Due to the tremendous negative pressures generated in the airway during inspiration, even slight weakness of one vocal fold will pull that vocal fold into the airway. A horse completely abducts its vocal folds during exercise so that the PCA muscle has to be tonically active at a high rate for minutes to hours. Also, in humans, unilateral paralysis mainly affects adduction, thus, adductory stimulation is the main target for unilateral paralysis in human. Adductory stimulation is much simpler because there are 4 times as much adductor muscles, their threshold is lower (so they can be stimulated separately simply by a lower amplitude), and they are anatomically situated superficially compare to the abductor muscles on the backside of the vocal cords.
In humans, U.S. Pat. No. 7,069,082 (incorporated herein by reference) describes laryngeal stimulation for vocal cord paralysis in the case of synkinetic reinnervated muscles. Other laryngeal stimulation patents for vocal cord paralysis stress the diagnosis of denervated vocal cord muscles. For example, in human sleep apnea, the muscles and their innervating nerves are intact. But laryngeal hemiplegia in horses is a different mechanism in which an ongoing distal axonopathy stops vocal fold movement in a position just lateral to the midline—there is no synkinetic reinnervation and denervation is the end stage, but then the stimulation via the nerve no longer works. In contrast, the transmission of natural signals via the nerve seems to be comprised, because the muscle does not move during any stage of exercise for a relatively long time (grade IV) or only in the condition of intensive exercise (grade III), but the muscle can be activated maximally (as in a non-diseased horse) via electrical stimulation of the nerve.
As the disorder in horses is due to loss of axons, most horses presenting with immobile vocal folds would be expected to have decreased or absent motor neurons. Therefore reanimation of the vocal fold with electrical stimulation would need to be directed at the denervated PCA muscle. Direct muscle stimulation is difficult under any circumstances, and larger muscles such as those in the horse have more technical problems.
In addition, any device for the treatment of the equine condition must not only be effective, it also must conform to the rules of the governing bodies that oversee equine sports. In thoroughbred racing, this requires that the device must not give the horse an unfair advantage. In addition, it cannot allow tampering with the horse's performance. Specifically, as wagering is an integral part of the sport, there cannot be a way of adjusting the device to manipulate the horse's performance.
As used herein, the term “paralysis” is used to refer to complete loss of nerve supply to a muscle, whereas “paresis” is used to refer to weakness of a muscle due to decreased motor nerve supply or activity, and “synkinesis” refers to inappropriate co-contraction of antagonistic muscles.